The present invention is concerned with 1H-indazole-3-acetic acid derivatives and their pharmaceutically-acceptable esters and salts. By means of their inhibition of the aldose reductase enzyme, these compounds are useful in the treatment of diabetic complications.
Compounds, such as sorbinil (S-6-fluorospiro[chroman-4,4'-imidazoline]-2',5'-dione; Sarges, U.S. Pat. No. 4,130,714), which have aldose reductase inhibitory activity, are of value in controlling certain chronic complications arising from diabetes mellitus (e.g., diabetic cataracts and neuropathy).
Non-hydantoin compounds previously reported to inhibit aldose reductase include 1H-benz[d,e]isoquinoline-1,3(2H)-dione-2-acetic acid derivatives, Sestanj et al., U.S. Pat. No. 3,821,383; halogen substituted chroman-4-carboxylic and chroman-4-acetic acids, Belletire, U.S. Pat. No. 4,210,663; spiro[chroman-4,5'-oxazolidin]-2',3'-diones, Schnur, U.S. Pat. No. 4,200,642; and variously substituted phthalazin-1(2H)-on-4-acetic acids, Larson et al., published European Patent Application No. 222,576.
Variously substituted 1-benzyl-1H-indazole-3-carboxylic acids and specifically 1-(p-chlorobenzyl)-1H-3-acetic acid have been reported to be useful as antispermatogenic agents, Corsi et al., J. Med. Chem., vol 19, pp. 778-783 (1976).